A review on actuation principls for few cubic millimeter sized mobile micro-robots

Actuation systems for few cubic millimeter sized mobile autonomous robots are subject to severe constraints in terms of e.g. size, fabrication or power consumption. Also the onboard electronics has limited performance due to both size and power restrictions, so actuation voltages, currents and frequency should be minimized. Various principles of electrical to mechanical energy conversion will be presented (piezoelectric, polymer, electrostatic) and their performances compared considering the above mentioned constraints. For propulsion, a further mechanical to mechanical conversion is necessary to allow long strokes. We will compare four principles for this conversion: inertial drives, walking, inch-worm and propulsion based on asymmetrical friction forces. Solutions where the energy is not onboard but rather scavenged in the environment are also reviewed. These solutions try to circumvent the energy limitations but present some inconveniences, especially when several micro-robots have to be simultaneously steered and/or propelled

Piezoactuators for Miniature Robots

Challenges in the realisation of a miniature robot are both to handle the complexity of such a system, and to cope with effects of the actual reduction in physical size of all the parts. In particular, the mechanisms for locomotion have to be analysed. The main achievements presented in the thesis are the evaluation and the development of fabrication techniques for miniature multilayer piezoceramic actuators, the evaluation of different motion mechanisms for miniature robots, and the development of building techniques for piezo-based miniature robots. New piezoelectric drive units for miniature robots were designed and fabricated. To realize these monolithic devices, the fabrication technique for multilayer piezoceramic structures was further developed and evaluated with respect to the potential for miniaturisation. Introducing milling in the green state as a technique for shaping piezoceramic actuators gave a geometrical freedom without impairing the possibility of miniaturisation. A rapid prototype process was also developed. In this process, green machining in a milling machine was not only used to shape the multilayer structure, but also to pattern the internal electrodes. The first prototype was a multilayer telescopic actuator, which proved to have a displacement amplification of about 5 compared to a multilayer stack. The drive units were used to evaluate different motion mechanisms. Experiments showed that for a mass corresponding to a typical miniature robot, i.e. 1-10 g, it is possible to use both dynamic and quasistatic motion mechanisms. Artefacts due to vibrations were identified as the main reason for non-ideal behaviour when the movable mass is small. Design criteria for robots with small masses are presented. A tethered cm3 miniature robot for micromanipulation was successfully built. Application specific integrated circuits and two drive units were integrated with a particular building technique. Three-axial positioning and manipulating operations were demonstrated, allowing for a 5-axial movement of a tool

Bioassays on ultrasonically trapped microbead clusters in microfluidic systems

The handling of biochemically functionalised beads or particles is becoming increasingly important in µTAS. Bead-based analysis of e.g. proteins can be made sensitive due to the large active surface area and flexible by chemical design of the bead surface. We have developed a microfluidic device utilising an array of integrated and individually controlled ultrasonic microtransducers for particle trapping [1]. Particles inserted in the device are subjected to acoustic radiation forces [2] confining them at localised trapping sites. We would now, for the first time at an international conference, like to present a technique for performing bioassays on such ultrasonically trapped beads in microfluidic systems. The microfluidic device is shown in Fig. 1, where the piezoceramic ultrasonic transducers can be seen in the channel crossings in the insert. The device is designed as an acoustic resonator, to obtain localised standing acoustic waves at each transducer with essentially one pressure node in the middle of the 72 µm deep channel when operated near 10 MHz. This configuration is chosen to keep trapped particles away from the interior surfaces of the device, thus enabling fast switching of beads with a minimum in carry-over between assays. The fluidic chip, shown in Fig. 2, is designed to allow injection of microbeads, washing fluid and sample to the three trapping sites. It has been shown that the microbead clusters, as shown in Fig. 3, can be trapped at considerably high perfusion rates, up to 10 µl/min, Fig 4. As a model bioassay, 6.7 µm biotin-covered beads (PC-B-6.0, Gerlinde Kisker, Germany) were injected and transported to one tapping site using washing fluid (water). Activating the transducer trapped the beads. A solution of FITC-tagged avidin was perfused over the bead bed at 3 µl/min, using the corresponding orthogonal sample channel. After 100 s the sample flow was turned off and the bead trap was washed by perfusing water at 3 µl/min. The fluorescence response from the trapped bead clusters was monitored during the assay, and the result is shown in Fig. 5. After excess avidin was washed from the bead trap, a measured step response . indicated that avidin had bound to the beads. Finally the possibility of moving trapped microbeads between the individually controlled trapping sites in the device is shown in Fig. 6, where the transducers are activated sequentially while keeping the bead carrying washing fluid at 3 µl/min during the experiment. Work in the near future will be focused on optimising the device with respect to the bioassay performance, and in a longer perspective on expanding the concept to two dimensions to enable a new dynamic mode of generating bioanalytical arrays

Ultrasonic beadtrapping for bioassays

This paper proposes a new dynamic mode of generating bioanalytical arrays based on ultrasonic trapping of microbeads in microfluidic systems. As compared to disposable glass slide microarrays, the proposed technology utilises exchangeable microbeads as the solid phase on which bioassays are performed. The use of microbeads in biochemical analysis is advantageous due to the increased surface area and thus the high binding capacity as compared to planar solid surfaces. By the integration of ultrasonic microtransducers in a microfluidic system, we have proved that it is possible to trap and manipulate microbead clusters by making use of acoustic standing wave forces. Functionalised microbeads have been trapped and moved between well-defined positions in a microchannel, thus for the first time showing trapping of microbeads within a flow-through device with individually controlled trapping sites in an array format. A device with three acoustic trapping sites was fabricated and evaluated. The lateral extension of each trapping site was essentially determined by the corresponding microtransducer dimensions, 0.8 x 0.8 mm2. The flow-through volume was approximately 1 µl and the active trapping site volumes about 100 nl each. The strength of trapping was investigated, showing that 50 % of the initially trapped beads were still trapped at a perfusion rate of 10 µl/min. Since the beads determine the chemical functionality in the device a high degree of flexibility is expected. A fluorescence based avidin bioassay was successfully performed on biotin-coated microbeads trapped in the flow-through device, providing a first proof of principle of the proposed dynamic arraying concept. The dynamic arraying is believed to be expandable to two dimensions, thus with a prospect of performing targeted and highly parallel protein analysis in microfluidics

Trapping of microparticles in the near field of an ultrasonic transducer

We are investigating means of handling microparticles in microfluidic systems, in particular localized acoustic trapping of microparticles in a flow-through device. Standing ultrasonic waves were generated across a microfluidic channel by ultrasonic microtransducers integrated in one of the channel walls. Particles in a fluid passing a transducer were drawn to pressure minima in the acoustic field, thereby being trapped and confined at the lateral position of the transducer. The spatial distribution of trapped particles was evaluated and compared with calculated acoustic intensity distributions. The particle trapping was found to be strongly affected by near field pressure variations due to diffraction effects associated with the finite sized transducer element. Since laterally confining radiation forces are proportional to gradients in the acoustic energy density, these near field pressure variations may be used to get strong trapping forces, thus increasing the lateral trapping efficiency of the device. In the experiments, particles were successfully trapped in linear fluid flow rates up to 1 mm/s. It is anticipated that acoustic trapping using integrated transducers can be exploited in miniaturised total chemical analysis systems (μTAS), where e.g. microbeads with immobilised antibodies can be trapped in arrays and subjected to minute amounts of sample followed by a reaction, detected using fluorescence

Versatile microchip utilising ultrasonic standing waves

This paper presents the concept and initial work on a microfluidic platform for bead-based analysis of biological sample. The core technology in this project is ultrasonic manipulation and trapping of particle in array configurations by means of acoustic forces. The platform is ultimately aimed for parallel multistep bioassays performed on biochemically activated microbeads (or particles) using submicrolitre sample volumes. A first prototype with three individually controlled particle trapping sites has been developed and evaluated. Standing ultrasonic waves were generated across a microfluidic channel by integrated PZT ultrasonic microtransducers. Particles in a fluid passing a transducer were drawn to pressure minima in the acoustic field, thereby being trapped and confined laterally over the transducer. It is anticipated that acoustic trapping using integrated transducers can be exploited in miniaturised total chemical analysis systems (µTAS), where e.g. microbeads with immobilised antibodies can be trapped in arrays and subjected to minute amounts of sample followed by a reaction, detected using fluorescence. Preliminary results indicate that the platform is capable of handling live cells as well as microbeads. A first model bioassay with detection of fluorescein marked avidin binding to trapped biotin beads has been evaluated

Array transducer for ultrasonic manipulation of particles

This paper presents the concept and initial work on a microfluidic platform for bead-based analysis of biological sample. The core technology in this project is ultrasonic manipulation and trapping of particle in array configurations by means of acoustic forces. The platform is ultimately aimed for parallel multistep bioassays performed on biochemically activated microbeads (or particles) using submicrolitre sample volumes. A first prototype with three individually controlled particle trapping sites has been developed and evaluated. Standing ultrasonic waves were generated across a microfluidic channel by integrated PZT ultrasonic microtransducers. Particles in a fluid passing a transducer were drawn to pressure minima in the acoustic field, thereby being trapped and confined laterally over the transducer. It is anticipated that acoustic trapping using integrated transducers can be exploited in miniaturised total chemical analysis systems (µTAS), where e.g. microbeads with immobilised antibodies can be trapped in arrays and subjected to minute amounts of sample followed by a reaction, detected using fluorescence. A first model bioassay with detection of fluorescein marked avidin binding to trapped biotin beads has been evaluated. To enable development of the next generation of 2D array trapping devices, means of microfabricating multilayer ultrasonic array transducers using thick film technology have been developed

Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes)

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Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes)

Abstract: Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)\u2013defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52\u20131.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.Abstract: BACKGROUND: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). METHODS: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. RESULTS: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. CONCLUSIONS: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs